Maca compositions and methods of use

ABSTRACT

The present application is directed to composition comprising various maca extracts and the use of such compositions for treating certain diseases, disorders, and conditions.

INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/785,170 filed Oct. 16, 2017, which claims priority to of U.S.Provisional Application No. 62/411,977 filed Oct. 24, 2016, the contentsof each is incorporated by reference herein in its entirety.

BACKGROUND

The present disclosure relates to novel compositions of maca root(Lepidium meyenii, also called Peruvian Ginseng) and methods of usingsame. Such compositions may be used, for example, in improved methods ofincreasing libido, ameliorating sexual dysfunction caused byantidepressants, decreasing inflammation, increasing energy levels,increasing stamina, increasing athletic performance, improving memory,ameliorating discomfort related to menstruation, ameliorating thesymptoms of hormonal imbalances, HIV/AIDS, cancer (including discomfortdue to administration of chemotherapy to treat cancer), menopause,andropause, anemia, osteoporosis, and chronic fatigue syndrome,improving fertility, decreasing symptoms of tuberculosis, improving mood(for example, reducing depression), and increasing immune function.

More particularly, the present disclosure relates to the surprising andunexpected finding that particular combinations of maca root varietiesare more effective than other maca root varieties, alone or in othercombinations, at reducing inflammatory markers, such as cytokines, andthus may likely be more effective and/or provide more beneficial resultsto subjects ingesting the compositions disclosed herein than previousmaca root containing products.

Maca is used as a food, similar to sweet potatoes, but also has a numberof medicinal properties. Traditionally, maca is processed by boiling,baking, and drying the root, and then grinding the dried root materialinto powder. Various maca root powders are commercially available. Freshmaca roots have different colors due to genetic variations that resultin different phytochemical profiles in the different maca phenotypes.The different genotypes, reflected in root color phenotype includeyellow, red, purple, blue, black, and green. Yellow maca is the largestand sweetest-tasting, and are most commonly grown for food, while redand black maca are generally considered more medicinally potent, forexample, to reduce inflammation.

Inflammation is part of the non-specific immune response that occurs inreaction to bodily injury. Cytokines, amongst other factors, areregulators of the inflammatory process. Cytokines are small, secretedproteins with a specific effect on the interactions and communicationsbetween cells. There are both pro-inflammatory cytokines andanti-inflammatory cytokines.

Interleukin 6 (IL-6), for example, has broad physiological effects,including both pro- and anti-inflammatory properties, depending on thebiological context. IL-6 is implicated in numerous disease processes,including chronic inflammation, diabetes, and rheumatoid arthritis.While IL-6 is a promising target for clinical intervention, itscomplicated signal transduction pathway makes such interventionchallenging.

Inflammation can also lead to sexual problems (or sexual dysfunction).These conditions are widespread and adversely affect mood, well-being,and interpersonal relationships. Most sexual problems relate to sexualdesire (libido) in both females and males and male erectile dysfunction(ED). Current pharmacological interventions for the management of sexualproblems include drugs, intrapenile therapies, and penile prosthesisimplantation for males and hormonal therapy for females. Treatment ofsexual problems in females is also problematic, with pharmacologicaltreatments often resulting in severe, undesirable side-effects.Non-pharmacological treatments include vaginal electromyographybiofeedback, pelvic floor physical therapy, cognitive behaviouraltherapy, transcutaneous electrical nerve stimulation, andvestibulectomy. Post-menopausal women may also suffer from decreasedlibido, in part due to falling estrogen and testosterone levels.Decreased libido remains a significant sexual problem in both males andfemales.

SUMMARY

This application is based in part on the surprising discovery thatcertain maca root blends provide an unexpected increase in the reductionof the anti-inflammatory response of cells. In some aspects, the macaroot blends can be used to treat, ameliorate and/or prevent inflammatoryresponses. In some aspects, the maca root blends, disclosed herein, maybe used to increase libido and or to treat, ameliorate, or preventsymptoms of sexual dysfunction. After considering this discussion, andparticularly after reading the section entitled “Detailed Description”and the attached appendix (Appendix A, which is herein incorporated byreference in its entirety), one will understand how the features of thecompositions and methods disclosed herein provide advantages over otherknown compositions and methods.

Embodiments disclosed herein relate to compositions that comprise,consist essentially of, or consist of a mix of one or more maca roots.Such compositions may be used to, for example, to reduce an individual'sinflammatory response. In some aspects, the compositions include a macaroot blend of one or more phenotypes (color) of maca root. In someaspects, the one or more maca root phenotypes are pulverized into apowder. In some aspects, the composition includes a macamide-macamenemixture. In some embodiments, the maca roots used in the macacompositions are selected based on their macamide and/or macamenecontent.

Other embodiments disclosed herein relate to the use of suchcompositions. These compositions are useful for, inter alia, increasinganti-inflammatory properties and decreasing inflammatory cytokineproduction, which will necessarily affect the many pathways that areaffected by the anti-inflammatory pathway, including but not limited toincreasing libido and reducing the effects of chronic inflammation. Insome embodiments, the compositions disclosed herein may be useful fortreating or enhancing sex drive in individuals undergoing menopause orother hormonal imbalances.

Some embodiments provide a method for increasing sex drive inindividuals with hormonal imbalances. For example, a method may includeadministering an effective amount of a maca root blend to a subject. Thesubject's desire to engage in sexual activity may be increased relativeto providing no maca root or other maca root blends.

In another aspect, the embodiments relate to methods of treating asubject with the compositions disclosed herein. The terms “subject,”“patient” or “individual” as used herein refer to a vertebrate,preferably a mammal, more preferably a human. “Mammal” can refer to anyanimal classified as a mammal, including humans, domestic and farmanimals, and zoo, sport, or pet animals, such as, for example, horses,sheep, cows, pigs, dogs, cats, etc. Preferably, the mammal is human.

In some embodiments, the composition includes black maca root, yellowmaca root, red maca root, or any combination of the foregoing.

In some embodiments, a maca root blend comprises a combination of blackand yellow maca. In some embodiments, a maca root blend comprises somecombination of black and red maca. In some embodiments, a maca rootblend comprises some combination of red and yellow maca. In someembodiments, a maca root blend is a one to one ratio of two maca rootphenotypes. In some embodiments, a maca root blend is a two to one ratioof two maca root phenotypes. In some embodiments, a maca root blend is afour to one ratio of two maca root phenotypes.

Some embodiments are formulated as nutritional supplements. Suchsupplements may be formulated to be consumed daily. For example, themaca containing nutritional supplement may be formulated to deliverabout 1 to about 40 grams of maca root per day per individual subject.This can occur in one, two, three or more doses during the day and canoccur daily over a period of one, two, three or more days, or weeks, aswell as longer periods as would be envisaged by the skilled artisan.

In some embodiments, the maca root is present at an effective dose. Insome embodiments, the supplement is a solid. In some embodiments, thesolid is a powder. In some embodiments, the supplement is a liquid. Insome embodiments, the liquid is a concentrated formulation. In someembodiments, the supplement further comprises at least one of asweetener and a flavoring agent.

Some embodiments provide a method of making a composition comprising amaca root blend and excipients. The method may include boiling, baking,and drying the maca root and combining with some amount of excipients.

Some embodiments provide a method of making a composition comprising amaca root blend and excipients. In some embodiments, the composition isfurther formulated for oral administration to a subject.

In some embodiments, the nutritional supplement further comprises asecond agent. In some embodiments, the second agent is selected from ahormone, a non-steroidal anti-inflammatory agent, a vitamin, a mineral,and combinations of the foregoing.

Some embodiments provide compositions comprising an amount of black macaroot and an amount of red maca root, wherein the amounts have a ratio ofblack maca root to red maca root, and the ratio is from about 1:1 toabout 4:1. Some embodiments provide compositions comprising an amount ofblack maca root and an amount of red maca root, wherein the amounts havea ratio of black maca root to red maca root, and the ratio is from about1:1 to about 4:1. Some embodiments provide compositions comprising anamount of black maca root and an amount of yellow maca root, wherein theamount have a ratio of black maca root to yellow maca root, and theratio is from about 2:1 to 1:2.

Some embodiments provide methods of increasing libido in a subject inneed thereof, comprising co-administering a composition comprising asynergistically effective amount of black maca root and red maca root tothe subject. Some embodiments provide methods of increasing libido in asubject in need thereof, comprising co-administering a compositioncomprising a synergistically effective amount of black maca root andyellow maca root to the subject.

Some embodiments provide methods of decreasing cytokine activity in asubject in need thereof, comprising administering a compositioncomprising a synergistically effective amount of black maca root to redmaca root to the subject, wherein the cytokine is selected from IL-1β,IL-6, IL-8, and combinations thereof. Some embodiments provide methodsof decreasing cytokine activity in a subject in need thereof, comprisingadministering a composition comprising a synergistically effectiveamount of black maca root to yellow maca root to the subject, whereinthe cytokine is selected from IL-1β, IL-6, IL-8, IP-10, IL-4, IFN-γ, andcombinations thereof.

Some embodiments provide for use of compositions for improved treatmentof sexual dysfunction in humans, the composition comprising a firstamount of black maca root and a second amount of red maca root, thefirst and second amounts provided in a synergistic ratio. Someembodiments provide for use of compositions for improved treatment ofsexual dysfunction in humans, the composition comprising a first amountof black maca root and a second amount of yellow maca root, the firstand second amounts provided in a synergistic ratio.

Some embodiments provide compositions consisting essentially of anapproximately 1:4 ratio of black to red maca root for use in treatingsexual dysfunction. Some embodiments provide compositions comprising anamount of black maca root and an amount of yellow maca root, wherein theamounts have a ratio of black maca root to yellow maca root, and theratio is about 1:1. Some embodiments provide compositions consistingessentially of an approximately 1:1 ratio of black to yellow maca rootfor use in treating sexual dysfunction.

Some embodiments provide improved methods of increasing libido. Someembodiments provide improved methods of ameliorating sexual dysfunctioncaused by antidepressants. Some embodiments provide improved methods ofdecreasing inflammation. In some embodiments, these methods compriseproviding a composition comprising an effective amount of at least twoof black maca root, yellow maca root, and red maca root. In someembodiments the ratio of two of the phenotypes is from about 1:1 toabout 4:1.

Some embodiments provide improved methods of increasing energy levels.Some embodiments provide improved methods of increasing stamina. Someembodiments provide improved methods of increasing athletic performance.In some embodiments, these methods comprise providing a compositioncomprising an effective amount of at least two of black maca root,yellow maca root, and red maca root. In some embodiments the ratio oftwo of the phenotypes is from about 1:1 to about 4:1.

Some embodiments provide improved methods of improving memory. In someembodiments, these methods comprise providing a composition comprisingan effective amount of at least two of black maca root, yellow macaroot, and red maca root. In some embodiments the ratio of two of thephenotypes is from about 1:1 to about 4:1.

Some embodiments provide improved methods of ameliorating discomfortrelated to menstruation. Some embodiments provide improved methods ofameliorating the symptoms of hormonal imbalances. Some embodimentsprovide improved methods of ameliorating symptoms of menopause. Someembodiments provide improved methods of ameliorating symptoms ofandropause. Some embodiments provide improved methods of amelioratingsymptoms of osteoporosis. Some embodiments provide improved methods ofameliorating symptoms of improving fertility. In some embodiments, thesemethods comprise providing a composition comprising an effective amountof at least two of black maca root, yellow maca root, and red maca root,having a ratio. In some embodiments the ratio is from about 1:1 to about4:1.

Some embodiments provide improved methods of ameliorating symptoms ofHIV/AIDS. Some embodiments provide improved methods of amelioratingsymptoms of cancer. Some embodiments provide improved methods ofameliorating discomfort related to administration of chemotherapy totreat cancer. In some embodiments, these methods comprise providing acomposition comprising an effective amount of at least two of black macaroot, yellow maca root, and red maca root. In some embodiments the ratioof two of the phenotypes is from about 1:1 to about 4:1.

Some embodiments provide improved methods of ameliorating symptoms ofanemia. Some embodiments provide improved methods of amelioratingsymptoms of chronic fatigue syndrome. Some embodiments provide improvedmethods of decreasing symptoms of tuberculosis. Some embodiments provideimproved methods of improving mood (e.g., reducing depression). Someembodiments provide improved methods of increasing immune function. Insome embodiments, these methods comprise providing a compositioncomprising an effective amount of at least two of black maca root,yellow maca root, and red maca root. In some embodiments the ratio oftwo of the phenotypes is from about 1:1 to about 4:1.

Some embodiments provide improved mitochondrial function. Someembodiments provide improved methods of improving mitochondrialfunction. Some embodiments provide improved methods of increasingenergy. In some embodiments, these compositions and methods compriseproviding a composition comprising an effective amount of at least twoof black maca root, yellow maca root, and red maca root. In someembodiments the ratio of two of the phenotypes is from about 1:1 toabout 4:1.

Some embodiments provide compositions comprising an amount of black macaroot and an amount of red maca root, wherein the amounts have a ratio ofblack maca root to red maca root, and the ratio is from about 1:1 toabout 4:1.

Some embodiments provide methods of increasing libido in a subject inneed thereof, comprising co-administering a composition comprising asynergistically effective amount of black maca root and red maca root tothe subject.

Some embodiments provide methods of decreasing cytokine activity in asubject in need thereof, comprising administering a compositioncomprising a synergistically effective amount of black maca root to redmaca root to the subject, wherein the cytokine is selected from thegroup consisting of IL-1β, IL-6, IL-8, and combinations thereof.

Some embodiments provide methods of treating sexual dysfunction inhumans, comprising administering a composition comprising a first amountof black maca root and a second amount of red maca root, the first andsecond amounts provided in a synergistic ratio.

Some embodiments provide for use of a composition for improved treatmentof sexual dysfunction in humans, comprising administering a compositioncomprising a first amount of black maca root and a second amount of redmaca root, the first and second amounts provided in a synergistic ratio.

Some embodiments provide for use of a composition for reducing musclefatigue in a human, comprising administering a composition comprising afirst amount of black maca root and a second amount of red maca root,the first and second amounts provided in a synergistic ratio. Someembodiments provide for use of a composition for reducing mental fatiguein a human, comprising administering a composition comprising a firstamount of black maca root and a second amount of red maca root, thefirst and second amounts provided in a synergistic ratio. Someembodiments provide for use of a composition for increasing physicalperformance in a human, comprising administering a compositioncomprising a first amount of black maca root and a second amount of redmaca root, the first and second amounts provided in a synergistic ratio.In some embodiments, reducing physical, mental, or muscle fatigue may beduring periods of physical exertion. Some embodiments provide for use ofa composition as described herein for increasing a human's stamina suchas, but not limited to, physical stamina. Some embodiments provide foruse of a composition as described herein for increasing a human'scapacity to exert physical force, such as but not limited to duringexercise. Some embodiments provide for use of a composition as describedherein for increasing a human's aerobic working capacity. Someembodiments provide for use of a composition as described herein forincreasing a human's anaerobic working capacity. Some embodimentsprovide for use of a composition as described herein for increasing thelength of time for which a human can exert a physical force, such as butnot limited to, during exercise.

Some embodiments provide for use of a composition as described hereinfor reducing the effects of physical exertion in a human comprisingadministering a composition as described herein. Reducing effects mayinclude, but is not limited to, reducing lactate formation, reducingliver glycogen, reducing serum malondialdehyde, reducing musclemalondialdehyde, reducing liver malondialdehyde, reducing alanineaminotransferase, reducing aspartate aminotransferase, and/or decreasingcytokine activity. Reducing the effects of physical exertion may meanthat the effects experienced by a subject such as a human are reduced orameliorated during physical exertion or for a period afterward thatwould be readily ascertainable by the skilled artisan depending on thecontext in which this is used.

Some embodiments provide for use of a composition for reducing lactatein a human, comprising administering a composition comprising a firstamount of black maca root and a second amount of red maca root, thefirst and second amounts provided in a synergistic ratio. In certainembodiments, the reducing of lactate in a human can be during physicalexertion. In some embodiments, the lactate can be reduced by about 10 toabout 50%, about 15 to about 45%, about 25 to about 50%, about 20 toabout 50%, about 45%, about 50% and ranges therebetween.

Some embodiments provide for use of a composition for reducing liverglycogen in a human, comprising administering a composition comprising afirst amount of black maca root and a second amount of red maca root,the first and second amounts provided in a synergistic ratio. In certainembodiments, the reducing of liver glycogen in a human can be duringphysical exertion. In some embodiments, the liver glycogen can bereduced by about 10 to about 40%, about 15 to about 35%, about 25 toabout 35%, about 20 to about 40%, about 25%, about 35% and rangestherebetween.

Some embodiments provide for use of a composition for reducing serummalondialdeyhde (MDA) in a human, comprising administering a compositioncomprising a first amount of black maca root and a second amount of redmaca root, the first and second amounts provided in a synergistic ratio.In certain embodiments, the reduction of serum MDA in a human can beduring physical exertion. In some embodiments, the serum MDA can bereduced by about 20 to about 40%, about 25 to about 35%, about 20 toabout 35%, about 25%, about 35%, and ranges therebetween.

Some embodiments provide for use of a composition for reducing muscleMDA in a human, comprising administering a composition comprising afirst amount of black maca root and a second amount of red maca root,the first and second amounts provided in a synergistic ratio. In certainembodiments, the reduction of muscle MDA in a human can be duringphysical exertion. In some embodiments, the muscle MDA can be reduced byabout 15 to about 30%, about 20 to about 25%, about 20 to about 30%,about 25%, about 20% and ranges therebetween.

Some embodiments provide for use of a composition for reducing liver MDAin a human, comprising administering a composition comprising a firstamount of black maca root and a second amount of red maca root, thefirst and second amounts provided in a synergistic ratio. In certainembodiments, the reduction of liver MDA in a human can be duringphysical exertion. In some embodiments, the liver MDA can be reduced byabout 20 to about 25%, about 15 to about 25%, about 20 to about 30%,about 22%, about 23%, and ranges therebetween.

Some embodiments provide for use of a composition for increasing liversuperoxide dismutase (SOD) in a human, comprising administering acomposition comprising a first amount of black maca root and a secondamount of red maca root, the first and second amounts provided in asynergistic ratio. In certain embodiments, the increasing of liver SODin a human can be during physical exertion. In some embodiments, theliver SOD can be increased by about 5 to about 15%, about 5 to about10%, about 7%, about 10%, and ranges therebetween.

Some embodiments provide for use of a composition for increasing muscleSOD in a human, comprising administering a composition comprising afirst amount of black maca root and a second amount of red maca root,the first and second amounts provided in a synergistic ratio. In certainembodiments, the increasing of muscle SOD in a human can be duringphysical exertion. In some embodiments, the muscle SOD may be increasedby about 5 to about 10%, about 5 to about 15%, about 7 to about 10%,about 7%, about 6%, and ranges therebetween.

Some embodiments provide for use of a composition for increasing liverglutathione peroxidase (GSH-Px) in a human, comprising administering acomposition comprising a first amount of black maca root and a secondamount of red maca root, the first and second amounts provided in asynergistic ratio. In certain embodiments, the increasing of liverGSH-Px in a human can be during physical exertion. In some embodiments,the liver GSH-Px may be increased by about 2 to about 10%, about 3 toabout 5%, about 3 to about 8%, about 4%, about 6%, and rangestherebetween.

Some embodiments provide for use of a composition for increasing muscleGSH-Px in a human, comprising administering a composition comprising afirst amount of black maca root and a second amount of red maca root,the first and second amounts provided in a synergistic ratio. In certainembodiments, the increasing of muscle GSH-Px in a human can be duringphysical exertion. In some embodiments, the muscle GSH-Px is increasedby about 20 to about 50%, about 25 to about 30%, about 25 to about 45%,about 35 to about 50%, about 40 to about 50%, about 25%, about 45%,about 27%, about 44%, and ranges therebetween.

Some embodiments provide for use of a composition for reducing alanineaminotransferase (ALT) in a human, comprising administering acomposition comprising a first amount of black maca root and a secondamount of red maca root, the first and second amounts provided in asynergistic ratio. In certain embodiments, the reduction of ALT in ahuman can be during physical exertion. In some embodiments, the ALT canbe reduced by up to about 10%, about 5 to about 10%, about 10%, about5%, about 4%, about 1%, and ranges therebetween.

Some embodiments provide for use of a composition for reducing aspartateaminotransferase (AST) in a human, comprising administering acomposition comprising a first amount of black maca root and a secondamount of red maca root, the first and second amounts provided in asynergistic ratio. In certain embodiments, the reduction of AST in ahuman can be during physical exertion. In some embodiments, the AST canbe reduced by about 5 to about 20%, about 10 to about 20%, about 15 toabout 20%, about 13%, about 15%, and ranges therebetween.

Some embodiments provide for use of a composition for reducing totalcholesterol in a human, comprising administering a compositioncomprising a first amount of black maca root and a second amount of redmaca root, the first and second amounts provided in a synergistic ratio.In certain embodiments, the reduction of total cholesterol in a humancan be during physical exertion. In some embodiments, the totalcholesterol may be reduced by about 10 to about 25%, about 15 to about25%, about 20 to about 25%, about 20%, about 15%, about 22%, about 14%,and ranges therebetween.

Some embodiments provide for use of a composition for reducingtriglycerides in a human, comprising administering a compositioncomprising a first amount of black maca root and a second amount of redmaca root, the first and second amounts provided in a synergistic ratio.In certain embodiments, the reduction of triglycerides in a human can beduring physical exertion.

Some embodiments provide for use of a composition for reducing nuclearfactor NF-κB in a human, comprising administering a compositioncomprising a first amount of black maca root and a second amount of redmaca root, the first and second amounts provided in a synergistic ratio.In certain embodiments, the reduction of NF-κB in a human can be duringphysical exertion. In some embodiments, the NF-κB can be reduced byabout 15 to about 25%, about 10 to about 20%, about 20%, about 25%, andranges therebetween.

Some embodiments provide for methods for use of a composition asdescribed herein for regulating sirtuin pathways. Some embodimentsprovide for use of a composition for increasing SIRT-1 in a human,comprising administering a composition comprising a first amount ofblack maca root and a second amount of red maca root, the first andsecond amounts provided in a synergistic ratio. In certain embodiments,the increasing of SIRT-1 in a human can be during physical exertion. Insome embodiments, SIRT-1 can be increased by about 25 to about 50%, upto about 50%, about 25 to about 70%, about 25%, about 35%, about 45%,about 50%, about 60%, and ranges therebetween.

Some embodiments provide for use of a composition for increasingmitochondrial transcription factor A (TFAM) in a human, comprisingadministering a composition comprising a first amount of black maca rootand a second amount of red maca root, the first and second amountsprovided in a synergistic ratio. In certain embodiments, the increasingof TFAM in a human can be during physical exertion. In some embodiments,the TFAM is increased by about 25 to about 50%, up to about 50%, about25 to about 70%, about 25%, about 35%, about 45%, about 50%, about 60%,and ranges therebetween.

Some embodiments provide for use of a composition for increasing nuclearrespiratory factor 1 (Nrf-1) in a human, comprising administering acomposition comprising a first amount of black maca root and a secondamount of red maca root, the first and second amounts provided in asynergistic ratio. In certain embodiments, the increasing of Nrf-1 in ahuman can be during physical exertion. In some embodiments, the Nrf-1can be increased by about 50 to about 100%, about 25 to about 75%, about50 to about 75%, about 75 to about 100%, about 50%, about 75%, about100%, about 150%, about 100 to about 150%, about 200%, about 100 toabout 200%, about 200 to about 300%, about 200%, about 300%, and rangestherebetween.

Some embodiments provide for use of a composition for increasing nuclearfactor erythroid 2 (Nrf-2) in a human, comprising administering acomposition comprising a first amount of black maca root and a secondamount of red maca root, the first and second amounts provided in asynergistic ratio. In certain embodiments, the increasing Nrf-2 in ahuman can be during physical exertion. In some embodiments, the Nrf-2can be increased by about 25 to about 50%, up to about 50%, about 25 toabout 70%, about 25%, about 35%, about 45%, about 50%, about 60%, andranges therebetween.

Some embodiments provide for use of a composition for increasingperoxisome proliferator-activated receptor-gamma coactivator (PGC-1) ina human, comprising administering a composition comprising a firstamount of black maca root and a second amount of red maca root, thefirst and second amounts provided in a synergistic ratio. In certainembodiments, the increasing PGC-1 in a human can be during physicalexertion. In some embodiments, the PGC-1 is increased by about 25 toabout 50%, up to about 50%, about 25 to about 70%, about 25%, about 35%,about 45%, about 50%, about 60%, and ranges therebetween.

Some embodiments provide compositions consisting essentially of anapproximately 1:4 ratio of black to red maca root.

Some embodiments provide for use of a composition for improved treatmentof sexual dysfunction in humans, comprising administering a compositionconsisting essentially of an approximately 1:4 ratio of black to redmaca root.

Some embodiments provide compositions comprising an amount of black macaroot and an amount of yellow maca root, wherein the amounts have a ratioof black maca root to yellow maca root, and the ratio is about 1:1.

Some embodiments provide methods of increasing libido in a subject inneed thereof, comprising co-administering a composition comprising asynergistically effective amount of black maca root and yellow maca rootto the subject.

Some embodiments provide methods of decreasing cytokine activity in asubject in need thereof, comprising administering a compositioncomprising a synergistically effective amount of black maca root toyellow maca root to the subject, wherein the cytokine is selected fromthe group consisting of IL-1β, IL-6, IL-8, IP-10, IL-4, IFN-γ, andcombinations thereof.

Some embodiments provide methods of treating sexual dysfunction inhumans, comprising administering a composition comprising a first amountof black maca root and a second amount of yellow maca root, the firstand second amounts provided in a synergistic ratio.

Some embodiments provide for use of a composition for improved treatmentof sexual dysfunction in humans, comprising administering a compositioncomprising a first amount of black maca root and a second amount ofyellow maca root, the first and second amounts provided in a synergisticratio.

Some embodiments provide compositions consisting essentially of anapproximately 1:1 ratio of black to yellow maca root.

Some embodiments provide for use of a composition for improved treatmentof sexual dysfunction in humans, comprising administering a compositionconsisting essentially of an approximately 1:1 ratio of black to yellowmaca root.

A composition consisting essentially of an approximately 1:1 ratio ofblack to yellow maca root for use in treating sexual dysfunction.

A more complete understanding of the compositions, methods, and uses ofthe compositions, will be afforded to those skilled in the art, as wellas a realization of additional advantages and objects thereof, by aconsideration of the following detailed description and attachedappendix.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings and appendix disclose illustrative embodiments. They do notset forth all embodiments. Other embodiments may be used in addition orinstead. Understanding that these Figures and appendix depict onlyseveral embodiments in accordance with the disclosure and are not to beconsidered limiting of its scope; the disclosure will be described withadditional specificity.

FIG. 1 represents the changes in IL-1β levels in supernatants from PBMC(peripheral blood mononuclear cell) cultures treated with serialdilutions of test products for 24 hours in the presence of bacteriallipopolysaccharide (LPS). Data are shown as group averages plus or minusthe standard deviation from each duplicate data set, when compared tothe average cytokine production from cultures treated with LPS in theabsence of test products.

FIG. 2 represents the change in IL-4 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 3 represents the change in IL-6 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 4 represents the change in IL-8 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 5 represents the change in IL-10 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 6 represents the change in IFN-γ levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 7 represents the change in TNF-α levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 8 represents the change in RANTES (regulated on activation, normalT-cell expressed and secreted) levels in supernatants from PBMC culturestreated with serial dilutions of test products for 24 hours in thepresence of bacterial lipopolysaccharide (LPS). Data are shown as groupaverages plus or minus the standard deviation from each duplicate dataset, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 9 represents the change in IP-10 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 10 represents the change in IL-2 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 11 represents the change in mitochondrial function in PBMC culturestreated with serial dilutions of test products for 24 hours in thepresence of bacterial lipopolysaccharide (LPS). Data are shown as groupaverages plus or minus the standard deviation from each duplicate dataset, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 12 represents the increase in forced swimming time achieved by ratssubject to the protocol of Example 4. An increased forced swimming timewas measured after administration of a maca composition comprising blackmaca and red maca wherein the black maca and red maca were present in aratio of 4:1.

FIG. 13 represents the decrease in NF-κB measured in rats in theprotocol of Example 4. A decrease in NF-κB was measured afteradministration of a maca composition comprising black maca and red macawherein the black maca and red maca were present in a ratio of 4:1.

FIG. 14 represents the increase of SIRT-1 measured in rats in theprotocol of Example 4. An increase in SIRT-1 was measured afteradministration of a maca composition comprising black maca and red macawherein the black maca and red maca were present in a ratio of 4:1.

FIG. 15 represents the increase of mitochondrial transcription factor A(TFAM) measured in the rats in the protocol of Example 4. An increase inTFAM was measured after administration of a maca composition comprisingblack maca and red maca wherein the black maca and red maca were presentin a ratio of 4:1.

FIG. 16 represents the increase of nuclear respiratory factor 1 (Nrf-1)measured in the rats in the protocol of Example 4. An increase in Nrf-1was measured after administration of a maca composition comprising blackmaca and red maca wherein the black maca and red maca were present in aratio of 4:1.

FIG. 17 represents the increase of nuclear factor erythroid 2 (Nrf-2)measured in the rats in the protocol of Example 4. An increase in Nrf-2was measured after administration of a maca composition comprising blackmaca and red maca wherein the black maca and red maca were present in aratio of 4:1.

FIG. 18 represents the increase of peroxisome proliferator-activatedreceptor-gamma coactivator (PGC-1) measured in the rats in the protocolof Example 4. An increase in PGC-1 activity was measured afteradministration of a maca composition comprising black maca and red macawherein the black maca and red maca were present in a ratio of 4:1.

DETAILED DESCRIPTION Definitions

The terminology used in the description presented herein is not intendedto be interpreted in any limited or restrictive manner, simply becauseit is being utilized in conjunction with a detailed description ofcertain specific embodiments described herein. Furthermore, embodimentsdescribed herein can include several novel features, no single one ofwhich is solely responsible for its desirable attributes or which isessential to practicing the invention herein described. The meaningsascribed to various terms and phrases as used herein are illustrativelyexplained below. It is noted that precise meaning of a particular termor phrase may differ depending on the context in which it is used.

Embodiments disclosed herein relate to the use of compositionscomprising, consisting essentially of, or consisting of maca rootpowder. The maca root may be provided as red, yellow, or black maca, orcombinations thereof, including pharmaceutically acceptable salts,hydrates, solvates, or mixtures thereof for the treatment or preventionof inflammatory disorders.

The term “treating” or “treatment” does not necessarily mean total cure.Any alleviation of any undesired signs or symptoms of the disease to anyextent or the slowing down of the progress, or even prevention of thedisease or condition can be considered treatment. As used herein, theterm “providing” (a substance) refers to supplying, making available, oradministering the substance. As used herein, the term “subject”encompasses animals, preferably mammals, and most preferably humans. Theterm “subject” may be used interchangeably with “patient.”

Some embodiments provide compositions and methods of treating subjectswith compositions that comprise, consist essentially of, or consist ofan effective amount of maca. Some embodiments provide compositions andmethod of treating subjects with compositions that comprise, consistessentially of, or consist of an effective amount of maca and aneffective amount of a second agent.

A “maca composition,” as used herein, generally refers to a compositioncomprising at least two different maca root phenotypes (although it canrefer to a single maca root phenotype in certain embodiments), where thedifferent phenotypes are denoted by different colors resulting fromparticular compositional characteristics. Examples of maca compositionswith different phenotypes include but are not limited to yellow andblack, black and red, and red and yellow. In some aspects, the macacompositions may include different maca root phenotypes provided indifferent molar, weight, or volume ratios. Maca compositions may includered, black, purple, green, yellow, blue maca root phenotypes andcombinations thereof in ratios that would be envisaged by the skilledartisan in light of the disclosure contained herein.

The term “sexual dysfunction,” as used herein, refers to difficultyexperienced by a subject during any stage of a normal sexual activity,including but not limited to physical pleasure, desire, preference,arousal or orgasm. Sexual dysfunction also includes desiredisorders—lack of sexual desire or interest in sex; arousal disordersinability to become physically aroused or excited during sexualactivity; orgasm disorders delay or absence of orgasm (climax); and paindisorders—pain during intercourse.

Identifying an individual with a sexual dysfunction or in need oftreatment for sexual dysfunction or symptoms thereof, may include, forexample, identifying one or more of the following disorders inaccordance with the fourth edition of the Diagnostic and StatisticalManual of Mental Disorders: hypoactive sexual desire disorder, sexualaversion disorder, female sexual arousal disorder, male erectiledisorder, female orgasmic disorder, male orgasmic disorder, anorgasmia,dyspareunia, and/or vaginismus. Identifying an individual with a sexualdysfunction or in need of treatment for sexual dysfunction or symptomsthereof may be made by, or with the assistance of, a medicalprofessional. In some aspects, identifying an individual with a sexualdysfunction or in need of treatment for sexual dysfunction or symptomsthereof, includes self-identification by the patient.

The term “libido,” as used herein, refers to a subject's overall sexualdrive or desire for sexual activity. A subject in need of increasedlibido may include a person diagnosed or self-diagnosed with one or moresexual dysfunctions or disorders.

The term “mitochondrial function”, as used herein, refers to the asubject's mitochondria's ability to synthesize adenosine triphosphate(ATP), measured and determined by methods known those of skill in theart.

An “effective amount,” as used herein includes within its meaning anon-toxic but sufficient amount of a compound active ingredient orcomposition comprising the same for use in the embodiments disclosedherein to provide the desired therapeutic effect. The exact amount ofthe active ingredient disclosed herein required will vary from subjectto subject depending on factors such as the species being treated, theage and general condition of the subject, the severity of the conditionbeing treated, the particular agent being administered, the weight ofthe subject, and the mode of administration and so forth. Thus, anembodiment may not specify an exact “effective amount”. For any givencase; an appropriate “effective amount” may be envisaged by the skilledartisan in light of the context of the term and the disclosure containedherein.

The term “physical exertion” as used herein may refer to exercise, suchas but not limited to, anaerobic exercise, aerobic exercise,weight-lifting, cross-training, athletic competition, tasks involvingmuscular exertion (e.g., manual labor), and the like, along withcombinations of these. As used herein, “physical exertion” may refer tothese activities as are engaged in by a mammal, such as a human.“Physical exertion” can also refer to undesirable effects experienced bya mammal, such as a human, shortly after the activities described inthis paragraph. The meaning and scope of this term would be immediatelyenvisaged by the skilled artisan when considering the scope in which itis used.

In some aspects, “effective amount” of total maca root, provided as one,two or more phenotypes of maca, disclosed herein can be, for example 1mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg,145 mg/kg, 150 mg/kg, 155 mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg, 195 mg/kg, 200 mg/kg, or more,or any fraction in between of a maca root composition. Accordingly, insome embodiments, the effective amount of total maca root in acompositions disclosed herein can be about 1 mg to about 5 g, preferablyper day. For example, the amount of total maca root can be 1 mg, 10 mg,100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g,or more, or any range or amount in between any two of the precedingvalues. In some aspects, the “effective amount” of total maca root isabout 3 grams of maca root per day per individual, provided as two ormore phenotypes of maca, to the individual regardless of individual'sbody weight.

By way of example, an “effective amount” of black maca root disclosedherein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg,6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg,130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg,195 mg/kg, 200 mg/kg, or more, or any fraction in between of black macaroot. Accordingly, in some embodiments, the effective amount of blackmaca root in compositions disclosed herein can be about 1 mg to about 5g, preferably per day. For example, the amount of black maca root can be1 mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g,4.5 g, or 5 g, or more, or any range or amount in between any two of thepreceding values.

By way of example, an “effective amount” of red maca root disclosedherein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg,6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg,130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg,195 mg/kg, 200 mg/kg, or more, or any fraction in between of red macaroot. Accordingly, in some embodiments, the effective amount of red macaroot in compositions disclosed herein can be about 1 mg to about 5 g,preferably per day. For example, the amount of red maca root can beabout 1 mg to about 5 g, preferably per day. For example, the amount ofred maca root can be 1 mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more, or any range or amount inbetween any two of the preceding values.

By way of example, an “effective amount” of yellow maca root disclosedherein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg,6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg,130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg,195 mg/kg, 200 mg/kg, or more, or any fraction in between of yellow macaroot. Accordingly, in some embodiments, the effective amount of yellowmaca root in compositions disclosed herein can be about 1 mg to about 5g, preferably per day. For example, the amount of yellow maca root canbe about 1 mg to about 5 g, preferably per day. For example, the amountof yellow maca root can be 1 mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g,2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more, or any range or amountin between any two of the preceding values.

By way of example, an “effective amount” of blue maca root disclosedherein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg,6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg,130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg,195 mg/kg, 200 mg/kg, or more, or any fraction in between of blue macaroot. Accordingly, in some embodiments, the effective amount of bluemaca root in compositions disclosed herein can be about 1 mg to about 5g, preferably per day. For example, the amount of blue maca root can beabout 1 mg to about 5 g, preferably per day. For example, the amount ofblue maca root can be 1 mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more, or any range or amount inbetween any two of the preceding values.

By way of example, an “effective amount” of purple maca root disclosedherein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg,6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg,130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg,195 mg/kg, 200 mg/kg, or more, or any fraction in between of purple macaroot. Accordingly, in some embodiments, the effective amount of purplemaca root in compositions disclosed herein can be about 1 mg to about 5g, preferably per day. For example, the amount of purple maca root canbe about 1 mg to about 5 g, preferably per day. For example, the amountof purple maca root can be 1 mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g,2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more, or any range or amountin between any two of the preceding values.

By way of example, an “effective amount” of green maca root disclosedherein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg,6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg,130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg,195 mg/kg, 200 mg/kg, or more, or any fraction in between of green macaroot. Accordingly, in some embodiments, the effective amount of greenmaca root in compositions disclosed herein can be about 1 mg to about 5g, preferably per day. For example, the amount of green maca root can beabout 1 mg to about 5 g, preferably per day. For example, the amount ofgreen maca root can be 1 mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more, or any range or amount inbetween any two of the preceding values.

Examples of the therapeutically effective amounts listed above, can, insome embodiments be administered in the methods described elsewhereherein on an hourly basis, e.g., every one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two,twenty-three hours, or any interval in between, or on a daily basis,every two days, every three days, every four days, every five days,every six days, every week, every eight days, every nine days, every tendays, every two weeks, every month, or more or less frequently, asneeded to achieve the desired therapeutic effect.

As used herein, a “second agent” refers to an additional active compoundor compounds (i.e., not excipients, diluents, or vehicles). Exemplarysecond agents include vitamins, minerals, hormones, non-steroidalanti-inflammatories, and anti-depressants.

In some embodiments, the maca composition is provided in combinationwith a second agent, e.g., within a single dosage form, such as a singleoral dosage form or an oral suspension dosage form. In some embodiments,the maca composition is provided with a second agent in a multi-unitdosage form. In some embodiments, the maca composition is providedsuspended in a solution of the second agent. Accordingly, providedherein are compositions that comprise, consist essentially of, orconsist of maca and a second agent.

The terms “macamide” and “macamene,” as used herein refer to specificclasses of compounds found in maca roots.

The term “physiologically acceptable” defines a carrier, diluent orexcipient that does not abrogate the biological activity and propertiesof the compound.

As used herein, a “carrier” refers to a compound that facilitates theincorporation of a compound into cells or tissues. For example, withoutlimitation, dimethyl sulfoxide (DMSO) is a commonly utilized carrierthat facilitates the uptake of many organic compounds into cells ortissues of a subject.

As used herein, a “diluent” refers to an ingredient in a compositionthat lacks pharmacological activity but may be pharmaceuticallynecessary or desirable. For example, a diluent may be used to increasethe bulk of a potent drug whose mass is too small for manufacture and/oradministration. It may also be a liquid for the dissolution of a drug tobe administered by injection, ingestion or inhalation. A common form ofdiluent in the art is a buffered aqueous solution such as, withoutlimitation, phosphate buffered saline that mimics the composition ofhuman blood.

As used herein, an “excipient” refers to an inert substance that isadded to a pharmaceutical composition to provide, without limitation,bulk, consistency, stability, binding ability, lubrication,disintegrating ability etc., to the composition. A “diluent” is a typeof excipient.

The pharmaceutical compositions disclosed herein may be manufactured ina manner that is itself known, e.g., by means of conventional mixing,dissolving, granulating, dragee-making, levigating, emulsifying,encapsulating, entrapping or tableting processes. Additionally, theactive ingredients are contained in an amount effective to achieve itsintended purpose. Many of the compounds used in the pharmaceuticalcombinations disclosed herein may be provided as salts withpharmaceutically compatible counterions.

Multiple techniques of administering a compound exist in the artincluding, but not limited to, oral, rectal, topical, aerosol, injectionand parenteral delivery, including intramuscular, subcutaneous,intravenous, intramedullary injections, intrathecal, directintraventricular, intraperitoneal, intranasal and intraocularinjections.

Some embodiments provide maca compositions comprising at least two macaroot phenotypes. Some embodiments provide maca compositions comprisingat least three maca root phenotypes. Some embodiments provide macacompositions comprising at least four maca root phenotypes. Someembodiments provide maca compositions comprising at least five maca rootphenotypes. Some embodiments provide maca compositions comprising two,three, four, or five maca root phenotypes.

In some embodiments, a composition comprises an effective amount ofblack maca and an effective amount of yellow maca. In some embodiments,a composition comprises an effective amount of black maca and aneffective amount of red maca. In some embodiments, a compositioncomprises an effective amount of black maca and an effective amount ofpurple maca. In some embodiments, a composition comprises an effectiveamount of black maca and an effective amount of green maca. In someembodiments, a composition comprises an effective amount of black macaand an effective amount of blue maca.

In some embodiments, a composition comprises an effective amount of redmaca and an effective amount of yellow maca. In some embodiments, acomposition comprises an effective amount of red maca and an effectiveamount of green maca. In some embodiments, a composition comprises aneffective amount of red maca and an effective amount of purple maca. Insome embodiments, a composition comprises an effective amount of redmaca and an effective amount of blue maca.

In some embodiments, a composition comprises an effective amount of redmaca, an effective amount of yellow maca, and an effective amount ofblack maca.

In some embodiments, the maca root phenotypes are present in a ratio of1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, 1:30,1:40, 1:50, 1:1:1, 1:1:2, 1:1:3, 1:1:4, 1:1:5, 1:1:6, 1:1:7, 1:1:8,1:1:9, 1:1:10, 1:2:1, 1:2:2, 1:2:3, 1:2:4, 1:2:5, 1:2:6, 1:2:7, 1:2:8,1:2:9, 1:2:10, 1:3:1, 1:3:2, 1:3:3, 1:3:4, 1:3:5, 1:3:6, 1:3:7, 1:3:8,1:3:9, 1:3:10, 1:4:1, 1:4:2, 1:4:3, 1:4:4, 1:4:5, 1:4:6, 1:4:7, 1:4:8,1:4:9, 1:4:10, 1:5:1, 1:5:2, 1:5:3, 1:5:4, 1:5:5, 1:5:6, 1:5:7, 1:5:8,1:5:9, 1:5:10, 1:6:1, 1:6:2, 1:6:3, 1:6:4, 1:6:5, 1:6:6, 1:6:7, 1:6:8,1:6:9, 1:6:10, 1:7:1, 1:7:2, 1:7:3, 1:7:4, 1:7:5, 1:7:6, 1:7:7, 1:7:8,1:7:9, 1:7:10, 1:8:1, 1:8:2, 1:8:3, 1:8:4, 1:8:5, 1:8:6, 1:8:7, 1:8:8,1:8:9, 1:8:10, 1:9:1, 1:9:2, 1:9:3, 1:9:4, 1:9:5, 1:9:6, 1:9:7, 1:9:8,1:9:9, 1:9:10, 1:10:1, 1:10:2, 1:10:3, 1:10:4, 1:10:5, 1:10:6, 1:10:7,1:10:8, 1:109:9, 1:10:10, or any ratio in between.

In some embodiments, the maca compositions comprise 1:1 black-red macaroot. In some embodiments, the maca compositions comprise 2:1 black-redmaca root. In some embodiments, the maca compositions comprise 4:1black-red maca root. In some embodiments, the maca compositions comprise1:4 black-red maca root. In some embodiments, the maca compositionscomprise 1:1 black-yellow maca root. In some embodiments, the macacompositions comprise 1:1 yellow-red maca root.

The compositions may, if desired, be presented in a pack or dispenserdevice which may contain one or more unit dosage forms containing theactive ingredient. The pack may for example comprise metal or plasticfoil, such as a blister pack. The pack or dispenser device may beaccompanied by instructions for administration. The pack or dispensermay also be accompanied with a notice associated with the container inform prescribed by a governmental agency regulating the manufacture,use, or sale of pharmaceuticals, which notice is reflective of approvalby the agency of the form of the drug for human or veterinaryadministration. Such notice, for example, may be the labeling approvedby the U.S. Food and Drug Administration for prescription drugs, or theapproved product insert. Compositions that can include a compounddescribed herein formulated in a compatible pharmaceutical carrier mayalso be prepared, placed in an appropriate container, and labeled fortreatment of an indicated condition.

In some embodiments, the compositions provided herein are formulated forintradermal, intramuscular, intraperitoneal, intravenous, subcutaneous,intranasal, epidural, oral, sublingual, intranasal, intracerebral,intravaginal, transdermal, rectal, ophthalmic, or topical delivery. Thepreferred mode of administration is left to the discretion of thepractitioner, and will depend in part upon the site of the medicalcondition. In most instances, administration will result in the releaseof the compounds of the embodiments disclosed herein into thebloodstream.

In some embodiments, the compositions provided herein comprise, consistessentially of, or consist of a combination of an effective amount ofmaca, which can be any one of, or combinations of, the phenotypesdescribed herein. In embodiments, compositions provided herein comprise,consist essentially of, or consist of a combination of a synergisticallyeffective amount of maca, which can be any one of, or combinations of,the phenotypes described herein.

In some embodiments, maca is provided with a nutritionally acceptablecarrier or a pharmaceutically acceptable carrier. As used herein, thephrase “nutritionally acceptable carrier”, “nutritionally acceptableexcipient”, “pharmaceutically acceptable carrier”, or “pharmaceuticallyacceptable excipient” refers to nutritionally or pharmaceuticallyacceptable materials, compositions or vehicles, suitable foradministering compounds of the embodiments disclosed herein to mammals.The carriers can include liquid or solid filler, diluent, excipient,solvent or encapsulating material, involved in carrying or transportingthe subject agent from one organ, or portion of the body, to anotherorgan, or portion of the body. Carriers can be “acceptable” in the senseof being compatible with the other ingredients of the formulation andnot injurious to the patient. Some examples of materials which can serveas nutritionally or pharmaceutically acceptable carriers include, butare not limited to: sugars, such as lactose, glucose and sucrose;starches, such as corn starch and potato starch; cellulose, and itsderivatives, such as sodium carboxymethyl cellulose, ethyl cellulose andcellulose acetate; powdered tragacanth; malt; gelatin; talc; excipientssuch as cocoa butter and suppository waxes; oils, such as peanut oil,cottonseed oil, safflower oil, sesame oil, olive oil, corn oil andsoybean oil; glycols, such as propylene glycol; polyols, such asglycerin, sorbitol, mannitol and polyethylene glycol; esters, such asethyl oleate and ethyl laurate; agar; buffering agents, such asmagnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-freewater; isotonic saline; Ringer's solution; ethyl alcohol; phosphatebuffer solutions; and other non-toxic compatible substances employed inpharmaceutical formulations. In some embodiments, the nutritionally orpharmaceutically acceptable carrier can be suitable for intravenousadministration. In some embodiments, the nutritionally orpharmaceutically acceptable carrier can be suitable for locoregionalinjection.

The term “composition” refers to pharmaceutically and nutraceuticallyacceptable preparation, and includes preparations suitable foradministration to subjects, e.g., humans. When the compounds of theembodiments disclosed herein are administered to subjects, e.g., humans,they can be given by itself or as a composition containing, for example,0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredients incombination with a nutritionally or pharmaceutically acceptable carrier.The amount of active agents incorporated into the multiple unit dosageform of the embodiments disclosed herein is quantum sufficiat to achievethe desired effect.

For oral administration, the compositions disclosed herein can beprovided as a tablet, aqueous or oil suspension, dispersible powder orgranule, emulsion, hard or soft capsule, syrup, elixir, chew, orbeverage. Solid dosage forms such as tablets and capsules may becomprise an enteric coating. Compositions intended for oral use can beprepared according to any method known in the art for the manufacture ofcompositions and such compositions may include one or more of thefollowing agents: sweeteners, flavoring agents, coloring agents,coatings, and preservatives. The sweetening and flavoring agents willincrease the palatability of the preparation. Tablets containing thecomplexes in admixture with non-toxic pharmaceutically acceptableexcipients suitable for tablet manufacture are acceptable.Pharmaceutically acceptable vehicles such as excipients are compatiblewith the other ingredients of the formulation (as well as non-injuriousto the patient). Such excipients include inert diluents such as calciumcarbonate, sodium carbonate, lactose, calcium phosphate or sodiumphosphate; granulating and disintegrating agents, such as corn starch oralginic acid; binding agents such as starch, gelatin or acacia; andlubricating agents such as magnesium stearate, stearic acid or talc.Tablets can be uncoated or can be coated by known techniques to delaydisintegration and absorption in the gastrointestinal tract and therebyprovide a sustained action over a longer period of time. For example, atime delay material such as glyceryl monostearate or glyceryl distearatealone or with a wax can be employed.

Formulations for oral use can also be presented as hardgelatin-containing or non-gelatinous capsules wherein the activeingredient is mixed with an inert solid diluent, for example calciumcarbonate, calcium phosphate or kaolin, or as soft gelatin capsuleswherein the active ingredient is mixed with water or an oil medium, suchas peanut oil, liquid paraffin or olive oil. Aqueous suspensions cancontain the complex of the described herein admixed with excipientssuitable for the manufacture of aqueous suspensions. Such excipientsinclude suspending agents, dispersing or wetting agents, one or morepreservatives, one or more coloring agents, one or more flavoring agentsand one or more sweetening agents such as sucrose or saccharin.

A chewable dosage form can be made with candy bases such as rice syrup,maltitol syrup, sugar/corn syrup, etc. The base can either contain sugaror be sugarless. Additives such as palm oil, sunflower oil, soylecithin, and glycerin can be included to formulate the chewable dose.The chewable can be flavored using natural and/or artificial flavors.

Oil suspensions can be formulated by suspending the active ingredient ina vegetable oil, such as arachis oil, olive oil, sesame oil or coconutoil, or in a mineral oil such as liquid paraffin. The oil suspension cancontain a thickening agent, such as beeswax, hard paraffin or cetylalcohol. Sweetening agents, such as those set forth above, and flavoringagents can be added to provide a palatable oral preparation. Thesecompositions can be preserved by an added antioxidant such as ascorbicacid. Dispersible powders and granules suitable for preparation of anaqueous suspension by the addition of water provide the activeingredient in admixture with a dispersing or wetting agent, a suspendingagent, and one or more preservatives. Additional excipients, for examplesweetening, flavoring and coloring agents, can also be present.

Syrups and elixirs can be formulated with sweetening agents, such asglycerol, sorbitol or sucrose. Such formulations can also contain ademulcent, a preservative, a flavoring or a coloring agent.

It will be appreciated that the amount of the compound may be combinedwith a carrier material to produce a single dosage form. Such forms willvary depending upon the host treated and the particular mode ofadministration.

When administered to a subject, e.g., to an animal for veterinary use orfor improvement of livestock, or to a human for therapeutic use, thecompositions disclosed herein are administered in isolated form or asthe isolated form in a therapeutic composition. As used herein,“isolated” means that the compositions disclosed herein are separatedfrom other components of either (a) a natural source, such as a plant orcell or food, preferably bacterial culture, or (b) a synthetic organicchemical reaction mixture. Preferably, via conventional techniques, thecompositions disclosed herein are purified. As used herein, “purified”means that when isolated, the isolate contains at least 95%, preferablyat least 98% of the composition.

Aqueous suspensions may contain the compound disclosed herein inadmixture with excipients suitable for the manufacture of aqueoussuspensions. Such excipients include suspending agents, dispersing orwetting agents, one or more preservatives, one or more coloring agents,one or more flavoring agents and one or more sweetening agents such assucrose or saccharin.

Controlled release vehicles are well known to those of skill in thepharmaceutical sciences. The technology and products in this art arevariably referred to as controlled release, sustained release, prolongedaction, depot, repository, delayed action, retarded release and timedrelease; the words “controlled release” as used herein is intended toincorporate each of the foregoing technologies.

Numerous controlled release vehicles are known, including biodegradableor bioerodable polymers such as polylactic acid, polyglycolic acid, andregenerated collagen. Known controlled release drug delivery devicesinclude creams, lotions, tablets, capsules, gels, microspheres,liposomes, ocular inserts, minipumps, and other infusion devices such aspumps and syringes. Implantable or injectable polymer matrices, andtransdermal formulations, from which active ingredients are slowlyreleased, are also well known and can be used in the disclosed methods.

Controlled release preparations can be achieved by the use of polymersto form complexes with or absorb the maca. The controlled delivery canbe exercised by selecting appropriate macromolecules such as polyesters,polyamino acids, polyvinylpyrrolidone, ethylenevinyl acetate,methylcellulose, carboxymethylcellulose, and protamine sulfate, and theconcentration of these macromolecule as well as the methods ofincorporation are selected to control release of active complex.

Controlled release of active complexes can be taken to mean any of theextended release dosage forms. The following terms may be considered tobe substantially equivalent to controlled release, for the purposes ofthe present disclosure: continuous release, controlled release, delayedrelease, depot, gradual release, long term release, programmed release,prolonged release, programmed release, proportionate release, protractedrelease, repository, retard, slow release, spaced release, sustainedrelease, time coat, time release, delayed action, extended action,layered time action, long acting, prolonged action, sustained actionmedications and extended release, release in terms of pH level in thegut and intestine, breakdown of the molecule and based on the absorptionand bioavailability.

Hydrogels, wherein maca powder is dissolved in an aqueous constituent togradually release over time, can be prepared by copolymerization ofhydrophilic mono-olefinic monomers such as ethylene glycol methacrylate.Matrix devices, wherein maca powder is dispersed in a matrix of carriermaterial, can be used. The carrier can be porous, non-porous, solid,semi-solid, permeable or impermeable. Alternatively, a device comprisinga central reservoir of maca powder surrounded by a rate controllingmembrane can be used to control the release of the complex. Ratecontrolling membranes include ethylene-vinyl acetate copolymer orbutylene terephthalate/polytetramethylene ether terephthalate. Use ofsilicon rubber or ethylene-vinyl alcohol depots are also contemplated.

Controlled release oral formulations are also well known. In oneembodiment, the active complex is incorporated into a soluble orerodible matrix, such as a pill or a lozenge. In another example, theoral formulations can be a liquid used for sublingual administration.These liquid compositions can also be in the form a gel or a paste.Hydrophilic gums, such as hydroxymethylcellulose, are commonly used. Alubricating agent such as magnesium stearate, stearic acid, or calciumstearate can be used to aid in the tableting process.

Embodiments of the compositions described herein may be administeredonce, twice, or three times per day. In some aspects, the compositionsare administered four times a day. For example, the compositions may beadministered before, after, or during a meal. Dosing for oraladministration may be with a regimen calling for single daily dose, orfor a single dose every other day, or for a single dose within 72 hoursof the first administered dose, or for multiple, spaced doses throughoutthe day. Active agents that can make up the therapy may be administeredsimultaneously, either in a combined dosage form or in separate dosageforms intended for substantially simultaneous oral administration. Theactive agents which make up the therapy may also be administeredsequentially, with either active component being administered by aregimen calling for two-step ingestion. Thus, a regimen may call forsequential administration of the active agents with spaced-apartingestion of the separate, active agents. The time period between themultiple ingestion steps may range from a few minutes to as long asabout 72 hours, depending upon the properties of each active agent suchas potency, solubility, bioavailability, plasma half-life and kineticprofile of the agent, as well as depending upon the age and condition ofthe patient. The active agents of the therapy whether administeredsimultaneously, substantially simultaneously, or sequentially, mayinvolve a regimen calling for administration of one active agent by oralroute and the other active agent by intravenous route. Whether theactive agents of the therapy are administered by oral or intravenousroute, separately or together, each such active agent will be containedin a suitable pharmaceutical formulation of pharmaceutically-acceptableexcipients, diluents or other formulations components.

Active ingredients (e.g., maca root and other pharmaceutical orsupplemental ingredients that may be present) can be administered by theoral route in solid dosage forms, such as tablets, capsules, andpowders, or in liquid dosage forms, such as elixirs, syrups, andsuspensions. Each active ingredient can be administered by theparenteral route in liquid dosage forms. The pharmaceutical compositionis preferably made in the form of a dosage unit containing a particularamount of each active ingredient.

In general, the pharmaceutical dosage forms of compositions of thisapplication can be prepared by conventional techniques, as are describedin Remington's Pharmaceutical Sciences, a standard reference in thisfield [Gennaro A R, Ed. Remington: The Science and Practice of Pharmacy.20^(th) Edition. Baltimore: Lippincott, Williams & Williams, 2000]. Fortherapeutic purposes, the active components of this combination therapyapplication are ordinarily combined with one or more adjuvantsappropriate to the indicated route of administration. The components maybe admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone,and/or polyvinyl alcohol, and then tableted or encapsulated forconvenient administration. Such capsules or tablets may contain acontrolled-release formulation as may be provided in a dispersion ofactive compound in hydroxypropyl methylcellulose. Solid dosage forms canbe manufactured as sustained release products to provide for continuousrelease of medication over a period of hours. Compressed tablets can besugar coated or film coated to mask any unpleasant taste and protect thetablet from the atmosphere, or enteric coated for selectivedisintegration in the gastrointestinal tract. Both the solid and liquidoral dosage forms can contain coloring and flavoring to increase patientacceptance. Other adjuvants and modes of administration are well andwidely known in the pharmaceutical art.

The compositions disclosed herein can preferably be formulated withother active ingredients such as a slow-acting agent or long actingagent in addition to drugs or alone before meals and/or after meals.Effective doses may be extrapolated from dose-response curves derivedfrom in vitro or animal model test systems. Such animal models andsystems are well known in the art.

Synergistic Compositions of Maca Root

In some embodiments, the compositions provided herein comprise asynergistically effective amount of maca phenotypes selected together toprovide a greater than additive effect. This greater than additiveeffect can include, but is not limited to, an increased libido and/ordecreased systemic inflammation. A “synergistically effective amount” asused herein refers to the amount of one component of a compositionnecessary to elicit a synergistic effect with another component presentin the composition. A “synergistic effect” as used herein refers to aresult that is unexpectedly superior than what would be expected wheneither component is administered alone. The exact synergisticallyeffective amounts of the active ingredients disclosed herein requiredwill vary from subject to subject depending on factors such as thespecies being treated, the age and general condition of the subject,co-morbidities, the severity of the condition being treated, theparticular agents being administered, the weight of the subject, and themode of administration, and so forth. Thus, embodiments may not specifyan exact “synergistic amount.” However, for any given case, anappropriate “synergistically effective amount” may be envisaged by theskilled artisan in light of the context of the term and the disclosurecontained herein.

By way of example, a “synergistically effective amount” of the blackmaca root disclosed herein can be, for example 01 mg/kg, 2 mg/kg, 3mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg,15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg,120 mg/kg, 125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150mg/kg, 155 mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg,185 mg/kg, 190 mg/kg, 195 mg/kg, 200 mg/kg, or more, or any fraction inbetween of black maca root. Accordingly, in some embodiments, thesynergistically effective amount of black maca root in compositionsdisclosed herein can be about 1 mg to about 5 g, preferably per day. Forexample, the amount of black maca root can be about 1 mg to about 5 g,preferably per day. For example, the amount of black maca root can be 1mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5g, or 5 g, or more, or any range or amount in between any two of thepreceding values.

By way of example, a “synergistically effective amount” of the red macaroot disclosed herein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg,20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg,125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg,190 mg/kg, 195 mg/kg, 200 mg/kg, or more, or any fraction in between ofred maca root. Accordingly, in some embodiments, the synergisticallyeffective amount of red maca root in compositions disclosed herein canbe about 1 mg to about 3 g, preferably per day. For example, the amountof red maca root can be about 1 mg to about 5 g, preferably per day. Forexample, the amount of red maca root can be 1 mg, 10 mg, 100 mg, 500 mg,1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more, or anyrange or amount in between any two of the preceding values.

By way of example, a “synergistically effective amount” of the yellowmaca root disclosed herein can be, for example 1 mg/kg, 2 mg/kg, 3mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg,15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg,120 mg/kg, 125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150mg/kg, 155 mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg,185 mg/kg, 190 mg/kg, 195 mg/kg, 200 mg/kg, or more, or any fraction inbetween of yellow maca root. Accordingly, in some embodiments, thesynergistically effective amount of yellow maca root in compositionsdisclosed herein can be about 1 mg to about 5 g, preferably per day. Forexample, the amount of yellow maca root can be about 1 mg to about 5 g,preferably per day. For example, the amount of yellow maca root can be 1mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5g, or 5 g, or more, or any range or amount in between any two of thepreceding values.

By way of example, a “synergistically effective amount” of the greenmaca root disclosed herein can be, for example 1 mg/kg, 2 mg/kg, 3mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg,15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg,120 mg/kg, 125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150mg/kg, 155 mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg,185 mg/kg, 190 mg/kg, 195 mg/kg, 200 mg/kg, or more, or any fraction inbetween of green maca root. Accordingly, in some embodiments, thesynergistically effective amount of green maca root in compositionsdisclosed herein can be about 1 mg to about 5 g, preferably per day. Forexample, the amount of green maca root can be about 1 mg to about 5 g,preferably per day. For example, the amount of green maca root can be 1mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5g, or 5 g, or more, or any range or amount in between any two of thepreceding values.

By way of example, a “synergistically effective amount” of the blue macaroot disclosed herein can be, for example 1 mg/kg, 2 mg/kg, 3 mg/kg, 4mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg,20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg,125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg,190 mg/kg, 195 mg/kg, 200 mg/kg, or more, or any fraction in between ofblue maca root. Accordingly, in some embodiments, the synergisticallyeffective amount of blue maca root in compositions disclosed herein canbe about 1 mg to about 5 g, preferably per day. For example, the amountof blue maca root can be about 1 mg to about 5 g, preferably per day.For example, the amount of blue maca root can be 1 mg, 10 mg, 100 mg,500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, or 5 g, or more,or any range or amount in between any two of the preceding values.

By way of example, a “synergistically effective amount” of the purplemaca root disclosed herein can be, for example 1 mg/kg, 2 mg/kg, 3mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg,15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg,120 mg/kg, 125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150mg/kg, 155 mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg,185 mg/kg, 190 mg/kg, 195 mg/kg, 200 mg/kg, or more, or any fraction inbetween of purple maca root. Accordingly, in some embodiments, thesynergistically effective amount of purple maca root in compositionsdisclosed herein can be about 1 mg to about 5 g, preferably per day. Forexample, the amount of purple maca root can be about 1 mg to about 5 g,preferably per day. For example, the amount of purple maca root can be 1mg, 10 mg, 100 mg, 500 mg, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5g, or 5 g, or more, or any range or amount in between any two of thepreceding values.

In some embodiments, the composition comprises a synergisticallyeffective amount of black maca and a synergistically effective amount ofyellow maca. In some embodiments, the composition comprises asynergistically effective amount of black maca and a synergisticallyeffective amount of red maca. In some embodiments, the compositioncomprises a synergistically effective amount of black maca and asynergistically effective amount of yellow maca. In some embodiments,the composition comprises a synergistically effective amount of red macaand a synergistically effective amount of yellow maca.

In some embodiments, the composition comprises a synergisticallyeffective amount of red maca, a synergistically effective amount ofyellow maca, and a synergistically effective amount of black maca.Certain embodiments may comprise a synergistically effective amount ofyellow, red, black, green, blue, or purple mace and combinationsthereof.

In some embodiments, the maca root phenotypes present in asynergistically effective amount are present in a ratio of 1:1, 1:2,1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, 1:30, 1:40, 1:50,1:1:1, 1:1:2, 1:1:3, 1:1:4, 1:1:5, 1:1:6, 1:1:7, 1:1:8, 1:1:9, 1:1:10,1:2:1, 1:2:2, 1:2:3, 1:2:4, 1:2:5, 1:2:6, 1:2:7, 1:2:8, 1:2:9, 1:2:10,1:3:1, 1:3:2, 1:3:3, 1:3:4, 1:3:5, 1:3:6, 1:3:7, 1:3:8, 1:3:9, 1:3:10,1:4:1, 1:4:2, 1:4:3, 1:4:4, 1:4:5, 1:4:6, 1:4:7, 1:4:8, 1:4:9, 1:4:10,1:5:1, 1:5:2, 1:5:3, 1:5:4, 1:5:5, 1:5:6, 1:5:7, 1:5:8, 1:5:9, 1:5:10,1:6:1, 1:6:2, 1:6:3, 1:6:4, 1:6:5, 1:6:6, 1:6:7, 1:6:8, 1:6:9, 1:6:10,1:7:1, 1:7:2, 1:7:3, 1:7:4, 1:7:5, 1:7:6, 1:7:7, 1:7:8, 1:7:9, 1:7:10,1:8:1, 1:8:2, 1:8:3, 1:8:4, 1:8:5, 1:8:6, 1:8:7, 1:8:8, 1:8:9, 1:8:10,1:9:1, 1:9:2, 1:9:3, 1:9:4, 1:9:5, 1:9:6, 1:9:7, 1:9:8, 1:9:9, 1:9:10,1:10:1, 1:10:2, 1:10:3, 1:10:4, 1:10:5, 1:10:6, 1:10:7, 1:10:8, 1:109:9,1:10:10, or any ratio in between.

In some embodiments, the synergistic maca compositions comprise 1:1black-yellow maca root. In some embodiments, the synergistic macacompositions comprise 1:1 yellow-red maca root. In some embodiments, thesynergistic maca compositions comprise 1:1 black-red maca root. In someembodiments, the synergistic maca compositions comprise 2:1 black-redmaca root. In some embodiments, the synergistic maca compositionscomprise 4:1 black-red maca root. In some embodiments, the synergisticmaca compositions comprise 1:4 black-red maca root.

Examples of embodiments of compositions of synergistic combinations ofmaca are compared to the composition of prior art maca as shown in Table1 as follows:

TABLE 1 JDS Blend A JDS Blend B Natural Maca Y:B 1:1 Maca Y:B 1:1 MacaTotal Sugar (g/100 g) 30.6 34.9 12.3 Protein (g/100 g) 15 11.8 9.77Total Amino Acids 11598 9825 8869 (mg/100 g) pH 5.15 5.26 5.41 FreeFatty Acids as Oleic 0.36 0.34 0.86 (g/100 g) Total Polyphenols (Gallic367 407 204 Acid Equivalents) (mg/100 g) Glucosinolates by HPLC *(umol/g) Glucoalyssin 0.345 0.212 <0.2 4-hydroxyglucobrassicin 0.4860.254 <0.2 Gluctoropaeolin 12.9 7.77 3.98 Total Glucosinolates 567 339163 mg/100 g Total Glucosinolates umol/g 13.8 8.23 3.98

Compositions of a black and yellow maca synergistic combination arecomprised of certain components including, but not limited to, thoseshown in Table 1. Embodiments of the invention as disclosed hereincomprise particular isolated phenotypes of maca that are then combinedin particular ratios as set forth herein to achieve their unique andunexpectedly superior results than that which exists in the prior art.Without being bound by theory, the inventors have also determinedparticular ranges of components of certain maca compositions, which areproduced by the combination of certain isolated phenotyes, which aredifferent than that which exists in the prior art. These differences areevidenced by the uniquely developed compositions and by their uniquelyconfigured chemical compositions as described herein. In someembodiments, processing of the maca compositions can further be employedto achieve compositions including those shown in Table 1. In someembodiments, further processing may be employed (which may includeheating, or further extractions in water or alcohol) to alter (i.e.,increase or decrease) the particular components of the maca compositionssuch as those listed in Table 1. In certain embodiments a macacomposition comprises between about 15 and about 40 grams of total sugarper 100 grams of maca composition. In certain embodiments, a macacomposition can comprise about 15, about 20, about 25, about 30, about35, about 40, between about 25 and about 35, or between about 30 andabout 35 grams of total sugar per 100 grams of maca composition andranges therebetween. Some embodiments of a maca composition may comprisegreater than about 15 grams of total sugar per 100 g of macacomposition.

In certain embodiments, a maca composition comprises between about 10and about 15 grams of protein per 100 grams of maca composition. Incertain embodiments, a maca composition can comprise about 10, about 12,about 15, between about 10 and about 12, between about 12 and about 15,or between about 11 and about 15 grams of protein per 100 grams of macacomposition and ranges therebetween. Some embodiments of a macacomposition may comprise greater than about 10 grams of protein per 100grams of maca composition.

In certain embodiments, a maca composition comprises between about 9000and about 12000 mg of total amino acids per 100 grams of macacomposition. In certain embodiments, a maca composition comprises about9000, about 9750, about 9800, about 10000, about 11000, about 11500, orabout 12000 mg of total amino acids per 100 grams of maca composition,and ranges therebetween. In certain embodiments, a maca compositionbetween about 9800 and about 11750, between about 9500 and about 11500,between about 9000 and about 10000, or between about 10000 and about11600 mg of total amino acids per 100 grams of maca composition andranges therebetween. Certain embodiments of a maca composition maycomprise greater than about 9000 mg of total amino acids per 100 gramsof maca composition. Certain embodiments may comprise between about 3000mg and about 5000 mg of proline per 100 grams of maca composition.Certain embodiments may comprise between about 2500 mg and about 6000mg, between about 3500 mg and about 4500 mg of proline per 100 grams ofmaca composition and ranges therebetween.

In certain embodiments, a maca composition has a pH of less than about5.4. In certain embodiments, a maca composition can have a pH of betweenabout 5.1 and about 5.3, between about 5.15 and about 5.26, betweenabout 5.1 and about 5.4 and ranges therebetween.

In certain embodiments, a maca composition can comprise between about0.3 and about 0.8 grams of free fatty acids as oleic acid per 100 gramsof maca composition. In certain embodiments, a maca composition cancomprise between about 0.3 and about 0.4, between about 0.34 and about0.36, between about 0.35 and about 0.8, or between about 0.5 and about0.8 grams of free fatty acids as oleic acid per 100 grams of macacomposition and ranges therebetween. In certain embodiments, a macacomposition can comprise about 0.35, about 0.3, about 0.4, about 0.5, orabout 0.8 grams of free fatty acids as oleic acid per 100 grams of macacomposition and ranges therebetween. Some embodiments of a macacomposition may comprise less than about 0.8 grams of free fatty acidsas oleic acid per 100 grams of maca composition.

Certain embodiments of a maca composition can comprise a predeterminedamount of total polyphenols. In some embodiments, total polyphenols cancomprise gallic acid equivalents. In certain embodiments, a macacomposition can comprise between about 250 and about 450, between about250 and about 300, between about 250 and about 350, between about 350and about 400, between about 250 and about 375, or between about 350 andabout 415 mg of total polyphenols per 100 grams of maca composition andranges therebetween. In certain embodiments, a maca composition cancomprise about 250, about 350, about 365, about 375, about 400, or about415 mg of total polyphenols per 100 grams of maca composition and rangestherebetween. In some embodiments, a maca composition can comprisegreater than about 250 mg of total polyphenols per 100 grams of macacomposition.

In certain embodiments, a maca composition can comprise between about0.2 and about 0.35 umol of glucoalyssin per gram of maca composition. Incertain embodiments, a maca composition can comprise between about 0.2and about 0.3, between about 0.25 and about 0.35, or between about 0.30and about 0.35 umol of glucoalyssin per gram of maca composition andranges therebetween. In certain embodiments, a maca composition maycomprise about 0.2, about 0.3, or about 0.35 umol of glucoalys sin pergram of maca composition. In some embodiments, a maca composition cancomprise greater than about 0.2 umol of glucoalyssin per gram of macacomposition.

In certain embodiments, a maca composition can comprise between about0.2 and about 0.5 umol of 4-hydroxyglucobrassicin per gram of macacomposition. In certain embodiments, a maca composition can comprisebetween about 0.2 and about 0.3, between about 0.25 and about 0.5,between about 0.4 and about 0.5, between about 0.4 and about 0.49 orbetween about 0.30 and about 0.4 umol of 4-hydroxyglucobrassicin pergram of maca composition and ranges therebetween. In certainembodiments, a maca composition may comprise about 0.2, about 0.25,about 0.35 or about 0.49 umol of 4-hydroxyglucobrassicin per gram ofmaca composition and ranges therebetween. In some embodiments, a macacomposition can comprise greater than about 0.2 umol of4-hydroxyglucobrassicin per gram of maca composition.

In certain embodiments, a maca composition can comprise between about 5and about 13 umol of gluctoropaeolin per gram of maca composition. Incertain embodiments, a maca composition can comprise between about 7 andabout 13, between about 8 and about 13, between about 5 and about 8,between about 10 and about 13, or between about 12 and about 13 umol ofgluctoropaeolin per gram of maca composition and ranges therebetween. Incertain embodiments, a maca composition can comprise about 5, about 8,about 10, about 12, or about 13 umol of gluctoropaeolin per gram of macacomposition and ranges therebetween. In some embodiments, a macacomposition can comprise greater than about 5 umol of gluctoropaeolinper gram of maca composition.

In certain embodiments, a maca composition may comprise a predeterminedamount of glucosinolates. In some embodiments, the glucosinolates may beselected from the group consisting of glucoalyssin,4-hydroxyglucobrassicin, and gluctoropaeolin. In certain embodiments, amaca composition can comprise between about 200 and about 700 mg oftotal glucosinolates per 100 grams of maca composition. In certainembodiments, a maca composition can comprise between about 200 and about350, between about 330 and about 570, between about 500 and about 575,between about 500 and about 700, between about 600 and about 700, orbetween about 300 and about 350 mg of total glucosinolates per 100 g ofmaca composition and ranges therebetween. In some embodiments, a macacomposition can comprise about 200, about 340, about 350, about 500,about 570, about 575, about 600, about 650, or about 700 mg of totalglucosinolates per 100 g of maca composition and ranges therebetween. Incertain embodiments, a maca composition can comprise greater than about200 mg of total glucosinolates per 100 grams of maca composition.

In certain embodiments, a maca composition can comprise between about 5and about 14 umol of total glucosinolates per gram of maca composition.In certain embodiments, a maca composition can comprise between about 5and about 8, between about 8 and about 14, between about 8 and about8.25, between about 13 and about 14, or between about 8.5 and about 13.5umol of total glucosinolates per gram of maca composition and rangestherebetween. In some embodiments, a maca composition can comprise about5, about 8, about 8.5, about 8.25, about 13, or about 14, umol of totalglucosinolates per gram of maca composition and ranges therebetween. Insome embodiments, a maca composition can comprise greater than about 5umol of total glucosinolates per gram of maca composition.

The following Examples are provided for illustrative purposes and arenot in any way intended to limit the scope of the application or claims.

EXAMPLES

Aqueous and ethanolic extracts of processed maca roots and maca rootblends were obtained using standard extraction methods. The aqueousextracts, as shown in Table 2, were used in the following examples.Additional data can be found in Appendix A, which was attached to U.S.Application No. 62/411,977 and incorporated in its entirety, includingthe drawings.

TABLE 2 Maca Root Preparations Maca root Color/Blend Product handling 1.Maca root Black Aqueous 2. Maca root Red Aqueous 3. Maca root YellowAqueous 4. Maca blend Black/Red 2:1 blend Aqueous 5. Maca blendBlack/Red 4:1 blend Aqueous 6. Maca blend Black/Red 1:1 blend Aqueous 7.Maca blend Black/Red 1:4 blend Aqueous 8. Maca blend Black/Yellow 1:1blend Aqueous 9. Maca blend Red/Yellow 1:1 Aqueous

Example 1: Effects of Maca Compositions Under Inflammatory Conditions

Human peripheral blood mononuclear cell (PBMC) cultures were treatedwith the highly inflammatory bacterial lipopolysaccharide (LPS) from E.coli (positive control). The cultures were incubated for 24 hours, afterwhich the cells and the culture supernatants were harvested and used tomonitor the reactions in each culture. The supernatant from each culturewas used for testing of a panel of pro- and anti-inflammatory cytokinesand anti-viral chemokines, using a Luminex magnetic bead array and theMagPix® multiplexing system to test for selected cytokines, as shown inFIGS. 1-11.

The testing for cellular activation was performed such that alltreatments, including each dose of test product and each positive andnegative control, were tested in triplicate. The testing of cytokineproduction was tested in duplicate. The tests were performed on cellsfrom one healthy blood donor.

Average and standard deviation for each data set, as well as statisticalcomparison, were calculated using Microsoft Excel. Statistical analysisof the in vitro data was performed by comparison of the measures(duplicates for Luminex cytokine testing) for a specific test conditionto relevant controls. Tail: a two-tailed t-test was applied, because atest material may either induce or inhibit a specific assay outcome.Type: an independent, or ‘unpaired’, test was applied, because each cellculture is unique, positioned in different areas of a microplate withslightly different environmental exposures, and handling through theassay (such as pipetting), although uniform, was not identical.Statistical significance was indicated if p<0.05 and a high level ofsignificance was indicated if p<0.01.

The effects of maca roots and blends on PBMC cytokine production weretested following the protocol described above. Below is a table listingthe ten cytokines/chemokines, and a brief description of their majormode of action. Following this description are the results of thetesting on PBMC culture supernatants and after administering doses of0.5 mg/mL test product.

FIG. 1 represents the changes in IL-1β levels in supernatants from PBMC(peripheral blood mononuclear cell) cultures treated with serialdilutions of test products for 24 hours in the presence of bacteriallipopolysaccharide (LPS). Data are shown as group averages plus or minusthe standard deviation from each duplicate data set, when compared tothe average cytokine production from cultures treated with LPS in theabsence of test products.

FIG. 2 represents the change in IL-4 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 3 represents the change in IL-6 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 4 represents the change in IL-8 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 5 represents the change in IL-10 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 6 represents the change in IFN-γ levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 7 represents the change in TNF-α levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 8 represents the change in RANTES levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 9 represents the change in IP-10 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 10 represents the change in IL-2 levels in supernatants from PBMCcultures treated with serial dilutions of test products for 24 hours inthe presence of bacterial lipopolysaccharide (LPS). Data are shown asgroup averages plus or minus the standard deviation from each duplicatedata set, when compared to the average cytokine production from culturestreated with LPS in the absence of test products.

FIG. 11 represents the change in mitochondrial function in PBMC culturestreated with serial dilutions of test products for 24 hours in thepresence of bacterial lipopolysaccharide (LPS). These PBMC cultures wereexposed to six 4-fold serial dilutions of each product, starting at 2mg/mL. Testing conditions were performed in triplicate and culturesmaintained at 37° C. and 5% CO₂ for 24 hours. After the 24-hourincubation, cultures were processed in the colorimetric MTT assay. AnMTT assay utilizes a dye that changes color dependent on mitochondrialfunction, which is directly related to cellular metabolic activity andviability. Healthy cells metabolize the MTT dye and turn the culturespurple. When a reduction in color is measured, this is linked to reducedcellular viability, either as a result of direct killing, or inhibitionof mitochondrial function leading to cell death. In this case, ameasured increase in color is measured, which indicates an increasedmitochondrial function (energy production) because unstimulated PBMC donot undergo cell division in the 24-hour period and the increasedcolorimetric reading observed in several maca-treated cell cultures arelikely linked to direct effects on cellular energy production. Data areshown as group averages plus or minus the standard deviation from eachduplicate data set, when compared to the average cytokine productionfrom cultures treated with LPS in the absence of test products.

These results demonstrate that compositions comprising both 4:1 blackmaca root to red maca root and 1:1 black maca root to yellow maca rootpossess significant anti-inflammatory effects. For example, but notlimited to, reduction of IL-6 (0.02 g), IL-8 (both 0.5 and 0.02 g/L),and reduction of IL-10 were all stronger than for either black or redmaca root alone. Such results were not expected or predicted.

Example 2: Effects of Maca Compositions on Inflammation

A double-blind, randomized, parallel group dose-finding pilot study isconducted to compare a dose of an appropriate amount of a macacomposition per day as a daily regimen to a placebo control in 40outpatients (mean age 30; half females, half males) with diagnosedchronic inflammation and/or an autoimmune disease, disorder, orcondition. The compositions may, for example, include a predeterminedamount of maca per kg of a subjects' body weight. Subjects are requiredto have exhibited symptoms of chronic inflammation and/or an autoimmunedisease, disorder, or condition for at least six months prior toinitiating the trial, and may not have commenced any new medicationswithin six months of initiating the trial.

The subjects are divided into groups of eight, Groups A, B, C, D, and E.Group A is the control group, Group B receives yellow maca only, Group Creceives 1:1 black to red maca, Group D receives 4:1 black to red maca,and Group E receives 1:1 black to yellow maca. Blood samples are takenfrom each subject at week 0, week 1, week 4, week 8, week 12, and week16. Cytokine levels are measured in each sample. At each blood draw,subjects also complete a brief questionnaire regarding their symptoms.

Subjects in each group report mild to moderate alleviation of symptoms,with subjects in Group B reporting similar results to control Group A.Subjects in Groups C, D, report the most improvement in symptomsrelative to Groups A and B, with subjects in Group D reporting thegreatest improvement. Similarly, Groups C and D also have the largestdecrease in cytokine levels, particularly in IL-6 levels.

Example 3: Effects of Maca Compositions on Libido and Sexual Function

A double-blind, randomized, parallel group dose-finding pilot study isconducted to compare a dose of an appropriate amount of a macacomposition per day as a daily regimen (relative to placebo control) in40 outpatients (mean age 36; 17 females) with diagnosed sexualdysfunction. The compositions may, for example, include a predeterminedamount of maca per kg of a subjects' body weight. Subjects are requiredto meet at least one of the following criteria for at least 4 weeks: (1)inability to have an orgasm (anorgasmia) during sexual activity; (2)clinically significant orgasm delay with masturbation or intercoursethat, according to self-report, representing a meaningful delay andinterfering with sexual function compared with the subject's usual timeto achieve orgasm; (3) inability to attain or maintain until completionof sexual activity an adequate erection or lubrication swelling responseof sexual excitement that, according to self-report, interfered withsexual function compared to prior to antidepressant medication; (4)decreased libido according to self-report.

Exclusion criteria include: primary or prior diagnosis of a sexualdisorder; sexual dysfunction secondary to general underlying medicalcondition; no other current primary psychiatric disorder; alcohol orsubstance abuse or dependence within the past 6 months; recent majorsexual relationship changes, disruption, or turmoil ongoing oranticipated which are unrelated to their sexual dysfunction, HAM-D-17 orHAM-A score (either) >10; current use of other drugs for sexualdysfunction or other therapies or medications to treat sexualdysfunction; hormone replacement therapy, unless patient had been onstable dose of hormone therapy for at least 3 months prior to theantidepressant treatment, had no sexual dysfunction while on the samehormone therapy regimen, and there was no change in the hormonereplacement therapy during the study; pregnancy, lactation, or plans tobecome pregnant during the study; any clinically significant abnormalityof the screening physical examination; any medical or psychologicalcondition or social circumstances that would impair subject's ability toparticipate reliably in the study, or that may have increased the riskto subjects or others as a result of participating in the study;testosterone implant during 6 months prior to screening; receivingpsychosexual or other therapy for sexual dysfunction and not willing todiscontinue that treatment at screening; and/or subjects for whom sexualactivity was inadvisable.

The subjects are divided into groups of eight, Groups A, B, C, D, and E.Group A is the control group, Group B receives yellow maca only, Group Creceives 1:1 black to red maca, Group D receives 4:1 black to red maca,and Group E receives 1:1 black to yellow maca. The Arizona SexualExperience Scale (ASEX) and the Massachusetts General Hospital SexualFunction Questionnaire (MGH-SFQ) are used to measure sexual dysfunction.Subjects in Group B report similar results to control Group A. Subjectsin Groups C, D, report improved sexual function and libido relative toGroups A and B, with subjects in Group D reporting the greatestimprovement.

Example 4—Reduction of Fatigue and Improvement of Metabolic Activity

Rats were randomly divided into 4 groups with similar body weight asfollows: 1) control group (vehicle); 2) maca powder (40 mg/kg bodyweight), 3) Exercise; 4) Exercise+Maca powder (40 mg/kg body weight)where the groups administered a maca composition as described hereinwere given a maca composition comprising black and red maca at a ratioof 4:1. The control groups were treated with a similar volume of vehiclewithout any maca. Those groups receiving doses of maca powder receivedthe maca powder intragastrically in a volume of 0.2 g/10 mL once per dayfor 21 consecutive days. The control group were treated with a similarvolume of vehicle without any maca powder.

Rats were made to swim without loading for 10 min, twice a week, toaccustom them to swimming. On the 14th day of the experiment, theweight-loaded swimming test was employed to evaluate the effects of macapowder on the endurance capacity of mice along with determining theeffect on certain indicators related to physical exertion. 30 minutesafter the oral administration of maca powder or vehicle without macapowder, the rats were dropped individually into an acrylic plastic poolcontaining fresh water maintained at 27±1° C., approximately 35centimeters deep. The rats were loaded with a lead block, weighingapproximately 5% of their body weight, attached to the tail. Theswimming time to exhaustion was used as one index of the degree offatigue. The rats were considered to be exhausted when they could notkeep their nose out of the water within a 10 second period.

After the weight-loaded swimming test, the control and test rats wereorally administered for 7 more days with vehicle containing no maca andvehicle with the maca root composition, respectively. Thirty minutesafter the last dosing on the 21st day, each rat was sacrificedimmediately after 90 minutes swimming without load. The selection ofswimming time that leads to fatigue was according to methods known inthe prior art. Blood, liver, muscle and brain samples were collected.The levels of serum glucose, lactate (LD), lactate dehydrogenase (LDH),blood urea nitrogen (BUN), and the contents of liver glycogen wasmeasured using commercially available kits according to themanufacturer's instructions.

Immediately after the blood was collected, the brain, liver, and leftgastrocnemius muscle was quickly dissected out, and kept at −80° C.until analysis. Each tissue was homogenized in ice-cold normal saline.These tissue homogenates were centrifuged at 3000 rpm for 10 min at 4°C., and the supernatants were assessed for the antioxidant status.

The activities of superoxide dismutase (SOD) and glutathione peroxidase(GSH-PX), the contents of lipid peroxidation product malondialdehyde(MDA), were determined using commercially available kits according tothe manufacturer's protocol. SIRT1, mitochondrial transcription factor A(TFAM), NF-κB, and Nrf2 were analyzed by Western blot methods in musclesamples using methods known in the art.

TABLE 3 Experimental protocol Group I, N = 7/arm Group II, N = 7/armControl Exercise Control + Maca Powder Exercise + Maca Powder

Table 3 above presents the experimental protocol that was utilized. Thefollowing table summarizes the experimental results that were obtained.

TABLE 4 Experimental results obtained with administration of a black:redmaca composition with a ratio of 4:1. Groups Maca WL-FST + Maca ItemsControl Powder WL-FST Powder --P-- Initial BW, g 271.71 ± 4.05 272.43 ±3.32 271.43 ± 5.26 273.00 ± 2.06 0.991 Final BW, g 287.86 ± 6.21^(ab)291.57 ± 3.41^(a) 269.00 ± 4.99^(b) 275.57 ± 6.54^(ab) 0.024 Glucose,mg/dL  94.29 ± 1.92^(bc)  86.86 ± 1.97^(c) 109.57 ± 3.29^(a) 103.43 ±2.59^(ab) 0.0001 Lactate mg/dL  7.31 ± 0.53^(c)  7.57 ± 0.36^(c)  21.89± 1.36^(a)  12.74 ± 1.07^(b) 0.0001 Creatine,  0.44 ± 0.05  0.48 ± 0.06 0.52 ± 0.07  0.58 ± 0.17 0.771 mg/dL BUN, mg/dL  7.71 ± 0.54  7.61 ±0.34  7.79 ± 0.32  7.97 ± 0.44 0.941 ALT, U/L  78.29 ± 3.26  75.43 ±2.42  77.57 ± 2.55  76.71 ± 3.62 0.917 AST, U/L 112.43 ± 6.98 109.57 ±6.83 117.43 ± 7.26 111.71 ± 4.26 0.849 T-C, mg/dL  53.43 ± 3.15  50.14 ±6.50  54.14 ± 2.98  51.29 ± 2.33 0.890 TG, mg/dL  60.86 ± 5.15  57.57 ±4.53  59.43 ± 4.01  58.43 ± 2.33 0.950 Liver Glycogen,  20.43 ± 2.21^(a) 15.99 ± 1.33^(ab)  17.31 ± 1.45^(ab)  11.34 ± 1.19^(b) 0.005 mg/g SerumMDA,  0.71 ± 0.03^(c)  0.44 ± 0.04^(d)  1.60 ± 0.06^(a)  1.17 ± 0.04^(b)0.0001 μmol/L Muscle MDA,  1.57 ± 0.06^(c)  1.18 ± 0.05^(d)  2.53 ±0.06^(a)  2.04 ± 0.05^(b) 0.0001 nmol/g Liver MDA,  2.10 ± 0.11^(c) 1.64 ± 0.06^(d)  3.28 ± 0.10^(a)  2.52 ± 0.12^(b) 0.0001 nmol/g LiverSOD  85.64 ± 2.46^(ab)  91.47 ± 2.29^(a)  71.02 ± 2.08^(c)  78.22 ±2.58^(bc) 0.0001 Muscle SOD  79.40 ± 1.74^(ab)  84.89 ± 2.76^(a)  71.64± 1.14^(b)  75.79 ± 2.32^(b) 0.001 Liver GSH-Px 116.32 ± 2.28^(a) 120.93± 2.09^(a) 106.57 ± 2.06^(b) 113.08 ± 2.40^(ab) 0.001 Muscle GSH-Px 11.10 ± 0.38^(b)  14.08 ± 0.38^(a)  6.26 ± 0.11^(d)  8.99 ± 0.25^(c)0.0001 BW: Body weight; BUN: Blood urea nitrogen; ALT: Alanineaminotransferase; AST: Aspartate aminotransferase; T-C: TotalCholesterol; TG: Triglycerides; Data are means ± SE. Differentsuperscripts (a-d) indicate group mean differences (p < 0.05). WL:Weight loaded; FST: Forced swimming test; MDA: Malondialdehyde; SOD:Superoxide dismutase; GSH-Px: glutathione peroxidase.). WL: Weightloaded; FST: Forced swimming test Data are means ± SE. Differentsuperscripts (a-d) indicate group mean differences (p < 0.05).

The data in table 4 is given as mean±SEM. Sample size was calculatedbased on a power of 85% and a p value of 0.05. Given that assumption, asample size of seven per treatment was used. The data was analyzed usingthe GLM procedure of SAS (SAS Institute: SAS User's Guide: Statistics),which is known to one of skill in the art. The treatments were comparedusing ANOVA and student's unpaired t test; P<0.05 was consideredstatistically significant.

FIG. 12 represents the increase in forced swimming time achieved by ratssubject to the protocol of Example 4. An increased forced swimming timewas measured after administration of a maca composition comprising blackmaca and red maca wherein the black maca and red maca were present in aratio of 4:1.

FIG. 13 represents the decrease in NF-κB measured in rats in theprotocol of Example 4. A decrease in NF-κB was measured afteradministration of a maca composition comprising black maca and red macawherein the black maca and red maca were present in a ratio of 4:1.

FIG. 14 represents the increase of SIRT-1 measured in rats in theprotocol of Example 4. An increase in SIRT-1 was measured afteradministration of a maca composition comprising black maca and red macawherein the black maca and red maca were present in a ratio of 4:1.

FIG. 15 represents the increase of mitochondrial transcription factor A(TFAM) measured in the rats in the protocol of Example 4. An increase inTFAM was measured after administration of a maca composition comprisingblack maca and red maca wherein the black maca and red maca were presentin a ratio of 4:1.

FIG. 16 represents the increase of nuclear respiratory factor 1 (Nrf-1)measured in the rats in the protocol of Example 4. An increase in Nrf-1was measured after administration of a maca composition comprising blackmaca and red maca wherein the black maca and red maca were present in aratio of 4:1.

FIG. 17 represents the increase of nuclear factor erythroid 2 (Nrf-2)measured in the rats in the protocol of Example 4. An increase in Nrf-2was measured after administration of a maca composition comprising blackmaca and red maca wherein the black maca and red maca were present in aratio of 4:1.

FIG. 18 represents the increase of peroxisome proliferator-activatedreceptor-gamma coactivator (PGC-1) measured in the rats in the protocolof Example 4. An increase in PGC-1 activity was measured afteradministration of a maca composition comprising black maca and red macawherein the black maca and red maca were present in a ratio of 4:1.

The methods, compositions, and devices described herein are presentlyrepresentative of preferred embodiments and are exemplary and are notintended as limitations on the scope of the invention. Changes thereinand other uses will occur to those skilled in the art which areencompassed within the spirit of the invention and are defined by thescope of the disclosure. Accordingly, it will be apparent to one skilledin the art that varying substitutions and modifications can be made tothe invention disclosed herein without departing from the scope andspirit of the invention.

As used in the claims below and throughout this disclosure, by thephrase “consisting essentially of” means including any elements listedafter the phrase, and limited to other elements that do not interferewith or contribute to the activity or action specified in the disclosurefor the listed elements. Thus, the phrase “consisting essentially of”indicates that the listed elements are required or mandatory, but thatother elements are optional and may or may not be present depending uponwhether or not they affect the activity or action of the listedelements.

What is claimed is:
 1. A nutritional supplement comprising: an effective amount of a maca composition (Lepidium meyenii), wherein the maca composition consists of a synergistic combination of black maca and red maca in a ratio of about 1:1.
 2. The nutritional supplement of claim 1, wherein the nutritional supplement further comprises a coating.
 3. The nutritional supplement of claim 1, wherein the nutritional supplement is provided in a dosage form and the dosage form is a chewable dosage form.
 4. The nutritional supplement of claim 3, wherein the nutritional supplement further comprises an additive.
 5. The nutritional supplement of claim 4, wherein the additive is selected from the group consisting of palm oil, sunflower oil, soy lecithin, and glycerin.
 6. The nutritional supplement of claim 1, wherein the nutritional supplement is provided in a dosage form and the dosage form is selected from the group consisting of a hard gelatin containing capsule, a non-gelatinous capsule, a plant-derived capsule, a syrup, an elixir, aqueous suspension, or an oil suspension.
 7. A nutritional supplement comprising: an effective amount of maca composition (Lepidium meyenii), wherein the maca composition consists of a synergistic combination of black maca and red maca in a ratio of about 4:1 to about 1:4.
 8. The nutritional supplement of claim 7, wherein the nutritional supplement is provided in a dosage form and the dosage form is a chewable dosage form.
 9. The nutritional supplement of claim 7, wherein the nutritional supplement further comprises an additive.
 10. The nutritional supplement of claim 9, wherein the additive is selected from the group consisting of palm oil, sunflower oil, soy lecithin, and glycerin.
 11. The nutritional supplement of claim 7, wherein the nutritional supplement is provided in a dosage form and the dosage form is selected from the group consisting of a hard gelatin containing capsule, a non-gelatinous capsule, a plant-derived capsule, a syrup, an elixir, aqueous suspension, or an oil suspension.
 12. A nutritional supplement comprising: an effective amount of maca composition (Lepidium meyenii), wherein the maca composition consists of a synergistic combination of red maca and yellow maca in a ratio of about 1:1.
 13. A method of treatment comprising: administering a nutritional supplement to a subject wherein the nutritional supplement comprises a maca composition.
 14. The method of claim 13, wherein the maca composition consists of a combination of black maca and red maca.
 15. The method of claim 13, wherein the maca composition consists of a combination of black maca and yellow maca.
 16. The method of claim 13, wherein the treatment is for reducing the anti-inflammatory response of cells.
 17. The method of claim 13, wherein the treatment decreases cytokine production in the subject.
 18. The method of claim 13, wherein the cytokine is selected from the group consisting of IL-1β, IL-6, IL-8, IP-10, IL-4, IFN-γ, and combinations thereof.
 19. A method of using a nutritional supplement, wherein the nutritional supplement comprises a maca composition consisting of an effective amount of a synergistic combination of maca phenotypes; and wherein the nutritional supplement is administered to a subject.
 20. The method of claim 19, wherein the nutritional supplement is used for reducing the subject's inflammatory response.
 21. The method of claim 19, wherein the nutritional supplement is used for decreasing cytokine production.
 22. The method of claim 19, wherein the nutritional supplement is used for decreasing inflammatory cytokine production.
 23. The method of claim 19, wherein the cytokine is selected from the group consisting of IL-1β, IL-6, IL-8, IP-10, IL-4, IFN-γ, and combinations thereof.
 24. The method of claim 19, wherein the nutritional supplement is used for reducing the effects of chronic inflammation.
 25. The method of claim 19, wherein the nutritional supplement is used to ameliorate the effects of a subject wherein the effects are selected from the group consisting of discomfort related to menstruation, the symptoms of menopause, the symptoms of andropause, the symptoms of HIV, the symptoms of anemia, discomfort related to chemotherapy, the symptoms of tuberculosis, the symptoms of osteoporosis, and combinations thereof.
 26. The method of claim 19, wherein the nutritional supplement is used to increase libido.
 27. The method of claim 19, wherein the nutritional supplement is used to increase immune function.
 28. The method of claim 19, wherein the nutritional supplement is used to improve fertility.
 29. The method of claim 19, wherein the nutritional supplement is used to increase immune function.
 30. The method of claim 19, wherein the nutritional supplement is used to improve the subject's mood.
 31. The method of claim 19, wherein the nutritional supplement is used to increase energy levels.
 32. The method of claim 19, wherein the nutritional supplement is used to increase stamina.
 33. The method of claim 19, wherein the nutritional supplement is used to increase athletic performance.
 34. The method of claim 19, wherein the nutritional supplement is used to ameliorate the symptoms of a hormonal imbalance.
 35. The method of claim 19, wherein the nutritional supplement is used to increase mitochondrial function.
 36. The method of claim 19, wherein the nutritional supplement is used to treat sexual dysfunction in the subject.
 37. A method of manufacturing a nutritional supplement, comprising: providing a maca composition; and forming the nutritional supplement as a dosage form suitable for oral consumption.
 38. The method of claim 37, wherein the forming comprises providing a base selected from the group consisting of palm oil, sunflower oil, soy lecithin, and glycerin.
 39. The method of claim 37, wherein the nutritional supplement is formed as a chewable dose.
 40. The method of claim 37, wherein the forming comprises forming a tablet.
 41. The method of claim 37, wherein the forming comprises forming a capsule.
 42. The method of claim 37, further comprising the step of coating the nutritional supplement.
 43. The method of claim 42, wherein the coating comprises soy lecithin. 